Identification and characterization of murine adipose tissue-derived somatic stem cells of Shenque (CV8) acupoint.

BACKGROUND: Shenque (CV8) acupoint is located on the navel and has been therapeutically used for more than 2000 years in Traditional Chinese Medicine (TCM). However, clinical research on the underlying therapeutic molecular mechanisms of the CV8 acupoint lags far behind. This study aimed to study the mechanisms of umbilical acupoint therapy by using stem cells. METHODS: The morphological characteristics of CV8 acupoint were detected under a stereomicroscope using hematoxylin and eosin (H&E) staining. Oil Red, Masson, and immunohistochemical staining on multi-layered slices were used to identify the type of cells at the CV8 acupoint. Cell proliferation was measured by a cell counting kit-8 (CCK-8) method. Flow cytometry and immunohistochemistry were used for cell identification. Induced differentiation was used to compare the differentiation of cells derived from CV8 acupoint and non-acupoint somatic stem cells into other cell types, such as osteogenic, adipogenic, and neural stem cell-like cells. RESULTS: Morphological observations showed that adipose tissues at the linea alba of the CV8 acupoint in mice had a mass-like distribution. Immunohistochemical staining confirmed the distribution of stem cell antigen-1 (Sca-1) positive cells in the multi-layered slices of CV8 acupoint tissues. Cells isolated from adipose tissues at the CV8 acupoint exhibited high expression of Sca-1 and CD44 and low expression of CD31 and CD34, and these cells possessed osteogenic, adipogenic, and neurogenic stem cell-like cell differentiation ability. The cell proliferation (day 4: 0.5138 ±â€Š0.0111 vs. 0.4107 ±â€Š0.0180, t = 8.447, P = 0.0011; day 5: 0.6890 ±â€Š0.0070 vs. 0.5520 ±â€Š0.0118, t = 17.310, P < 0.0001; day 6: 0.7320 ±â€Š0.0090 vs. 0.6157 ±â€Š0.0123, t = 13.190, P = 0.0002; and day 7: 0.7550 ±â€Š0.0050 vs. 0.6313 ±â€Š0.0051, t = 42.560, P < 0.0001), adipogenic ([9.224 ±â€Š0.345]% vs. [3.933 ±â€Š1.800]%, t = 5.000, P = 0.0075), and neurogenic stem cell-like cell differentiation (diameter < 50 µm: 7.2000 ±â€Š1.3040 vs. 2.6000 ±â€Š0.5477, t = 7.273, P < 0.0001; diameter 50-100 µm: 2.6000 ±â€Š0.5477 vs. 1.0000 ±â€Š0.7071, t = 4.000, P = 0.0039; and diameter >100 µm: 2.6000 ±â€Š0.5477 vs. 0.8000 ±â€Š0.8367, t = 4.025, P = 0.0038) were significantly enhanced in somatic stem cells derived from the CV8 acupoint compared to somatic stem cells from the groin non-acupoint. However, cells possessed significantly weaker osteogenicity ([2.697 ±â€Š0.627]% vs. [7.254 ±â€Š0.958]%, t = 6.893, P = 0.0023) in the CV8 acupoint group. CONCLUSIONS: Our study showed that CV8 acupoint was rich with adipose tissues that contained abundant somatic stem cells. The biological examination of somatic stem cells derived from the CV8 acupoint provided novel insights for future research on the mechanisms of umbilical therapy.

Effects of aerobic exercise, traditional Chinese exercises, and meditation on depressive symptoms of college student: A meta-analysis of randomized controlled trials.

BACKGROUND: Non-pharmacological intervention methods such as rehabilitation training or psychological treatment are mostly used in the treatment of depression owing to the limitation of adverse reactions such as drug treatment. However, the best non-pharmacological treatment strategy for depression in college students is unclear. Therefore, it is significant to discover non-drug intervention methods that can improve the depression symptoms of college students. METHOD: Electronic databases as of Sep 15, 2019, were searched, and reference lists and pharmaceutical dossiers were reviewed to detect published and unpublished studies from the date of their inception to Sep 15, 2019. With document quality evaluations and data extraction, Meta-Analysis was performed using a random effect model to evaluate the intervention effect of the aerobic exercise, traditional Chinese exercises, and meditation. RESULTS: A total of 44 original studies were included. The random effect model was used to combine the effect values with Standard Mean Difference (SMD), and the results were: aerobic exercise [SMD = -0.53, 95% CI (-0.77, -0.30), I2 = 80%, P < .001], traditional Chinese exercises [SMD = -0.42, 95% CI (-0.74, -0.10), I2 = 90%, P = .01], meditation [SMD = -0.51, 95% CI (-0.90, -0.12), I2 = 79%, P = .01]. There was greater heterogeneity among the included studies: aerobic exercise (I2 = 80%, P < .001), traditional Chinese medicine methods (I2 = 90%, P < .001), and meditation (I2 = 79%, P < .001). CONCLUSIONS: This study revealed that the depression symptoms of college students can be effectively improved by aerobic exercise, traditional Chinese exercises, and meditation. Aerobic exercise would have a better effect on anxiety and stress while traditional Chinese exercise would have a better effect on stress. Further research (such as high-quality randomized controlled trials and long-term follow-up) is required to evaluate the effects of aerobic exercise, traditional Chinese exercise, and meditation on the depressive symptoms of college students to further apply complementary and alternative therapies. ETHICS AND DISSEMINATION: The results of the effects of aerobic exercise, traditional Chinese exercises, and meditation on depressive symptoms for a college student will be reported in a peer-reviewed publication. Hopefully, our findings from this meta-analysis can provide the most up-to-date evidence for the contribution to preventing the occurrence of depressive symptoms in college students.

Ethyl acetate extract from Jiedu Xiaozheng Yin inhibits the proliferation of human hepatocellular carcinoma cells by suppressing polycomb gene product Bmi1 and Wnt/ß-catenin signaling.

Jiedu Xiaozheng Yin (JXY) is a Chinese herbal decoction used to treat hepatocellular carcinoma (HCC). Previous studies have demonstrated that JXY can inhibit HCC cell proliferation via induction of G0/G1 phase arrest. In this study, we investigated whether the inhibitory effect of JXY on HCC cells is associated with the inhibition of the Wnt/ß­catenin pathway and the polycomb gene product Bmi1. Ethyl acetate extract from JXY (EE-JXY) was prepared. Methyl thiazolyl tetrazolium (MTT) and colony formation assays were used to measure cell proliferation. Immunofluorescence was used to analyze the expression and location of ß-catenin and Bmi1. Immunohistochemistry was used to examine the expression of proliferating cell nuclear antigen (PCNA), c-myc and cyclin D1. ß-catenin, Bmi1, c-myc, cyclin D1 and p16INK4A mRNA levels were detected by RT-PCR. The results demonstrated that EE-JXY inhibited the expression of PCNA, c-myc, cyclin D1 and Bmi1, and upregulated the expression of p16INK4A. We also found that EE-JXY could facilitate ß-catenin translocation from the cytoplasm and nuclei to the cytomembrane. Finally, suppression of cell proliferation and expression of Bmi1 and Wnt/ß-catenin by EE-JXY was confirmed in a mouse xenograft model of HCC. Thus, EE-JXY can inhibit the proliferation of HCC partially via suppression of the Bmi1 and Wnt/ß-catenin signaling pathways.

Fuzheng Qingjie recipe induces apoptosis in HepG2 cells via P38 MAPK activation and the mitochondria-dependent apoptotic pathway.

Fuzheng Qingjie (FZQJ) recipe is a polyherbal Chinese medicine capable of suppressing tumor growth and is used as an adjuvant therapy for various types of cancer. However, its anticancer mechanisms are yet to be fully elucidated. In the present study, we explored whether p38 mitogen-activated protein kinase (MAPK) was involved in FZQJ-mediated mitochondria-dependent apoptosis in human hepatocellular carcinoma cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to measure the viability of HepG2 cells. 4,6-Diamidino-2-phenylindole (DAPI) and Annexin-V fluorescein isothiocyanate (FITC) were used to analyze the apoptosis of HepG2 cells. The mitochondrial membrane potential (∆ψ) and phosphorylated P38 MAPK protein were examined by a flow cytometer following 5,5',6,6'-tetrachloro­1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1) and Alexa Fluor® 647 mouse anti-phosphorylated P38 MAPK antibody staining, respectively. The activation of caspase-9 and caspase-3 were measured using colorimetric assays. Additionally, Bcl-2 and Bax expression were examined using reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis. The results demonstrated that water extract of FZQJ was able to induce apoptosis of HepG2 cells in vitro. FZQJ-induced apoptosis was accompanied by the loss of ∆ψ, downregulation of Bcl-2 and upregulation of Bax expression, and the activation of caspase-3, -9 and P38 MAPK. These results indicated that FZQJ induced apoptosis in HepG2 cells at least via P38 MAPK activation and the mitochondria-dependent apoptotic pathway.

Application of serum pharmacology in evaluating the antitumor effect of Fuzheng Yiliu Decoction from Chinese medicine.

OBJECTIVE: To investigate the feasibility of serum pharmacology in evaluating the antitumor effect of Chinese medicine (CM) of Fuzheng Guben (supporting the healthy energy and strengthening the body's resistance to pathogens), the effects of Fuzheng Yiliu Decoction (FYD), a typical prescription of Fuzheng Guben, on proliferation and apoptosis of hepatoma cells in vitro were observed by two methods with serum pharmacology and traditional pharmacology, respectively. METHODS: HepG2 cells were treated with FYD-containing serum or crude FYD extract in vitro. The proliferation rate was determined by methyl thiazolyl tetrazolium (MTT) assay. Cell cycle and apoptosis rate was performed by flow cytometry. And the levels of interleukin-2 (IL-2) and tumor necrosis factor α (TNF-α) in FYD-containing serum were detected by radioimmunoassay. RESULTS: FYD-containing serum remarkably inhibited proliferation and induced apoptosis of hepatoma cells at least by promoting the production of IL-2 and TNF-α in vivo. On the contrary, crude FYD extract promoted the proliferation and did not induce cell apoptosis. CONCLUSION: The results by serum pharmacology were accordant with those of our previous animal and clinical trials which indicates that serum pharmacology is a reasonable and feasible method for the evaluation of the antitumor effect of herbs of Fuzheng Guben.

[Influence of Chinese herbal medicine Feitai Capsule on completion or delay of chemotherapy in patients with stage IIIB/IV non-small-cell lung cancer: a randomized controlled trial].

BACKGROUND: Chemotherapy completion rate can reflect the tolerance and compliance of patients to chemotherapy. Poor tolerance may result in delay or suspension of the comprehensive treatment plan, thus affect the efficacy of cancer treatment. Evaluating methods to improve the completion rate of chemotherapy and reduce the occurrence of delayed chemotherapy has gained increasing attention and is the significant area of study in the field of cancer treatment. Studies have shown that Chinese medicine combined with chemotherapy could improve the quality of life in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC). OBJECTIVE: To observe the effects of Feitai Capsule, a Chinese patent herbal drug, combined with chemotherapy in patients with stage IIIB/IV NSCLC. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 60 diagnosed stage IIIB/IV NSCLC patients from the Department of Oncology, Fuzhou General Hosipital of Najing Military Region were randomly divided into treatment group (30 cases) and control group (30 cases). Patients in the treatment group were treated with chemotherapy plus Feitai Capsule and patients in the control group only received chemotherapy. Both groups of patients were treated for 4 therapeutic cycles. MAIN OUTCOME MEASURES: The chemotherapy completion rate and the chemotherapy delay rate were observed in each cycle of treatment. The therapeutic efficacy was evaluated after 4 cycles. RESULTS: The chemotherapy completion rate was 96.42% in the treatment group, while that of the control group was 74.07%. The chemotherapy delay rate was 3.57% in the treatment group, while that of the control group was 14.8% (P=0.007 0). The disease control rate was 78.6% in the treatment group, while that of the control group was 59.3% (P=0.173 9). CONCLUSION: Feitai Capsule can increase the chemotherapy completion rate in patients with stage IIIB/IV NSCLC.

Water extract of Hedyotis Diffusa Willd suppresses proliferation of human HepG2 cells and potentiates the anticancer efficacy of low-dose 5-fluorouracil by inhibiting the CDK2-E2F1 pathway.

Hedyotis Diffusa Willd (HDW), a Chinese herbal medicine, has been widely used as an adjuvant therapy against various cancers, including hepatocellular carcinoma (HCC). However, the underlying anticancer mechanisms are yet to be elucidated. In the present study, the anticancer effects of HDW were evaluated and the efficacy and safety of HDW combined with low-dose 5-fluorouracil (5-FU) were investigated. HepG2 cells were cultured in vitro and nude mouse xenografts were established in vivo. The proliferation of HepG2 cells was measured using the MTT method and flow cytometry. The mRNA and protein expression levels of cyclin-dependent kinase 2 (CDK2), cyclin E and E2F1 were examined using relative quantitative real-time PCR and western blot analysis, respectively. The results showed that water extract of HDW remarkably inhibited HepG2 cell proliferation in a dose-dependent manner via arrest of HepG2 cells at the G0/G1 phase and induction of S phase delay. This suppression was accompanied by a great decrease of E2F1 and CDK2 mRNA expression. In addition, HDW remarkably potentiated the anticancer effect of low-dose 5-FU in the absence of overt toxicity by downregulating the mRNA and protein levels of CDK2, cyclin E and E2F1. Our findings support the use of HDW as adjuvant therapy of chemotherapy and suggest that HDW may potentiate the efficiency of low-dose 5-FU in treating HCC.

Effect of Feitai Capsule () on quality of life and progression-free survival of patients with unresectable non-small cell lung cancer.

OBJECTIVE: To examine the effect of a Chinese medicinal herbal formula (Feitai Capsule, ) on the quality of life (QOL) and progression-free survival (PFS) of patients with unresectable non-small cell lung cancer (NSCLC). METHODS: Sixty-two patients were randomly divided into the treatment group (31 cases) and the control group (31 cases). For the treatment group, 4 capsules (1.2 g/capsule) of Feitai Capsule were administered 3 times a day after meals for 3 weeks; then no drug was administered for 1 week. This schedule was continued for at least 3 more cycles (12 weeks totally). If there were no obvious toxic reactions, the treatment was extended. The patients were evaluated at least once every 8 weeks until progressive disease (PD). For the control group, the regular follow-up and evaluation were performed at least once every 8 weeks until PD. Clinical symptoms, objective response, physical constitution and energy, QOL, and PFS were evaluated regularly. Analysis of variance (ANOVA), a non-parametric test, and analysis of covariance were used to compare clinical features, amelioration of clinical symptoms, physical constitution and energy, and QOL. Kaplan-Meier analysis was used to compare the two-group PFS. RESULTS: Sixty patients finished the final evaluation, with 30 patients in each group. Baseline characters between groups were not significantly different (P>0.05). The control group had a 36.7% improvement in clinical symptoms, while the treatment group had a 73.3% improvement. This difference was statistically significant (Z= -2.632, P=0.008). The control group had a 26.7% improvement in the Karnofsky performance status (KPS), while the treatment group had a 53.4% improvement. This was also significantly different (Z=-2.182, P=0.029). A comparative analysis indicated a positive correlation (r=0.917, P<0.001). Compared with the control group, QOL in the treatment group was significantly improved, except in the social/family condition and doctor-patient relationship indicators. The PFS of the treatment group and control group were 6.23 months and 4.67 months, respectively (P=0.048). CONCLUSION: Feitai Capsule, a Chinese medicinal herbal treatment could improve the QOL and extend the PFS of the unresectable NSCLC patients.

Fuzheng Yiliu Granule inhibits the growth of hepatocellular cancer by regulating immune function and inducing apoptosis in vivo and in vitro.

OBJECTIVE: To study the inhibitory effect of Fuzheng Yiliu Granule (FYG) on hepatocellular cancer (HCC) and investigate the mechanism mediating its bioactivity. METHODS: H22 tumor-bearing ICR mice were treated with FYG [3.6 g/(kg·d)] for 5 days. Tumor volume and tumor weight, percentages of CD3(+), CD4(+), CD8(+), and natural killer (NK) cells in peripheral blood, tumor apoptosis and serum levels of interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α) were evaluated. FYG-containing serum was prepared from SD rats treated for 7 days [high dose 3.6 g/(kg·d); middle dose 1.8 g/(kg·d); low dose 0.9 g/(kg·d)]. Cell cycle, cell viability, and apoptosis were evaluated after HepG2 cell line was cultured in FYG-containing serum for 48 h. The levels of IL-2 and TNF-α in FYG-containing serum were also determined. RESULTS: FYG produced a potent antitumor effect (P<0.01) and induced marked apoptosis of the tumor tissue (P<0.05). Mice treated with FYG had higher percentages of CD3(+) and CD4(+) (P<0.05), and more NK cells (P<0.01) in the peripheral blood than those in the animals treated with normal saline. Mice receiving FYG had the highest serum levels of IL-2 and TNF-α (P<0.01). High-dose FYG-containing serum significantly decreased HepG2 cell viability, inhibited cell proliferation (P<0.05), and induced apoptosis (P<0.01). In addition, the levels of IL-2 and TNF-α of high-dose-containing serum were higher than the blank serum (P<0.01). CONCLUSION: FYG could inhibit HCC growth by regulating immune function and inducing apoptosis of tumor cells in vivo and in vitro.

[Effects of Feitai Capsule on quality of life in patients with advanced non-small-cell lung cancer: a randomized controlled trial].

BACKGROUND: Recently the maintenance therapy of non-small-cell lung cancer (NSCLC) patients who completed required treatment cycles has caused widespread interests in the medical field. Traditional Chinese medicine may be a useful complement in maintenance treatment of mid-to-late stage NSCLC. OBJECTIVE: To observe the effects of Feitai Capsule, a compound traditional Chinese herbal medicine for expelling blood stasis and phlegm, on the quality of life of the NSCLC patients as a maintenance treatment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 62 mid-to-late stage NSCLC patients from Fuzhou General Hospital of Nanjing Military Region were included and randomly divided into treatment group (31 cases) and control group (31 cases). Patients in the treatment group were treated with Feitai Capsule, and patients in the control group did not accept any intervention. Regular observations and follow-up were performed for patients in the two groups. MAIN OUTCOME MEASURES: Analysis of variance, nonparametric test, and analysis of covariance were used to compare clinical features, amelioration of clinical symptoms, physical constitution and energy, and quality of life. RESULTS: There were two dropouts and 60 valid cases. The baseline characteristics of the two groups were similar. In the treatment group, symptom response and physical energy level were improved by 36.6% (Z=-2.632, P=0.008) and 26.7%(Z=-2.182, P=0.029), respectively. There was a positive correlation between these two factors (r=0.917, P<0.001). The patients in treatment group had a significantly improved quality of life after treatment. No serious adverse events were observed. CONCLUSION: Feitai Capsule as maintenance treatment can improve the quality of life of the patients with mild-to-late stage NSCLC.